InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DAB2

Summary

InnateDB Protein

IDBP-478205.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DAB2

Protein Name

disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila)

Synonyms

DOC-2; DOC2;

Species

Homo sapiens

Ensembl Protein

ENSP00000426245

InnateDB Gene

IDBG-17973 (DAB2)

Protein Structure

UniProt Annotation

Function

Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containg non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor- mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin- mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr- 419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor. {ECO:0000269PubMed:11387212, ECO:0000269PubMed:12805222, ECO:0000269PubMed:16267015, ECO:0000269PubMed:16984970, ECO:0000269PubMed:19306879, ECO:0000269PubMed:21995445, ECO:0000269PubMed:22323290, ECO:0000269PubMed:22491013}.

Subcellular Localization

Cytoplasm. Cytoplasmic vesicle, clathrin- coated vesicle membrane. Membrane, clathrin-coated pit. Note=Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. During mitosis is progressively displaced from the membrane and translocated to the cytoplasm.

Disease Associations

Tissue Specificity

Expressed in deep invaginations, inclusion cysts and the surface epithelial cells of the ovary. Also expressed in breast epithelial cells, spleen, thymus, prostate, testis, macrophages, fibroblasts, lung epithelial cells, placenta, brain stem, heart and small intestine. Expressed in kidney proximal tubular epithelial cells (at protein level). {ECO:0000269PubMed:10340382, ECO:0000269PubMed:15134832, ECO:0000269PubMed:9620555}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 80 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	80 [view]
Protein-Protein	80 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0035615	clathrin adaptor activity
GO:0038024	cargo receptor activity
GO:0046332	SMAD binding

Biological Process

GO:0001934	positive regulation of protein phosphorylation
GO:0006915	apoptotic process
GO:0008283	cell proliferation
GO:0010718	positive regulation of epithelial to mesenchymal transition
GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0015031	protein transport
GO:0016055	Wnt signaling pathway
GO:0030511	positive regulation of transforming growth factor beta receptor signaling pathway
GO:0032091	negative regulation of protein binding
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0043066	negative regulation of apoptotic process
GO:0045807	positive regulation of endocytosis
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0060391	positive regulation of SMAD protein import into nucleus
GO:0060766	negative regulation of androgen receptor signaling pathway
GO:0061024	membrane organization
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:2000096	positive regulation of Wnt receptor signaling pathway, planar cell polarity pathway
GO:2000370	positive regulation of clathrin-mediated endocytosis
GO:2000643	positive regulation of early endosome to late endosome transport

Cellular Component

GO:0005730	nucleolus
GO:0005765	lysosomal membrane
GO:0005886	plasma membrane
GO:0005905	coated pit
GO:0030665	clathrin-coated vesicle membrane
GO:0043231	intracellular membrane-bounded organelle
GO:0070022	transforming growth factor beta receptor homodimeric complex
GO:0070062	extracellular vesicular exosome